Novel substituted tetrahydrotriazaacenaphthylene derivatives as potent CRF1 receptor antagonists

Bioorganic and Medicinal Chemistry Letters

Volumn 17, Issue 18, 2007, Pages 5218-5221

  Gentile, Gabriella ^a   Di Fabio, Romano ^a   Pavone, Francesca ^a   Sabbatini, Fabio Maria ^a   St Denis, Yves ^a   Zampori, Maria Grazia ^a   Vitulli, Giovanni ^a   Worby, Angela ^b  

^a GSK   (Italy)

^b GLAXOSMITHKLINE   (United Kingdom)

Author keywords

Anxiety; Corticotropin releasing factor; CRF1 antagonists; Depression

Indexed keywords

8 (2,4 DICHLOROPHENYL) 4 [2 METHOXY 1 (METHOXYMETHYL)ETHYLAMINO] 2,7 DIMETHYLPYRAZOLO[1,5 A][1,3,5]TRIAZINE; BUTYL[2,5 DIMETHYL 7 (2,4,6 TRIMETHYLPHENYL) 7H PYRROLO[2,3 D]PYRIMIDIN 4 YL]ETHYLAMINE; CORTICOTROPIN RELEASING FACTOR; CORTICOTROPIN RELEASING FACTOR ANTAGONIST; NEUROHORMONE; TETRAHYDROTRIAZAAPHTHYLENE DERIVATIVE; UNCLASSIFIED DRUG;

ALKYLATION; ANXIETY; ARTICLE; BRAIN; CHO CELL; CONTROLLED STUDY; DEPRESSION; DRUG BIOAVAILABILITY; DRUG POTENCY; DRUG STRUCTURE; DRUG SYNTHESIS; HUMAN; HUMAN CELL; IN VITRO STUDY; STRESS;

ADMINISTRATION, ORAL; HUMANS; NAPHTHALENES; RECEPTORS, CORTICOTROPIN-RELEASING HORMONE; RECOMBINANT PROTEINS;

EID: 34547936937     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2007.06.077     Document Type: Article

References (15)

1. Nemeroff C.B. J. Clin. Psychiatry 64 (2003) 3
2. Wale W., Spiess J., Rivier C., and Rivier J. Science 213 (1981) 1394
3. Owen M.J., and Nemeroff C.B. Pharmacol. Rev. 43 (1991) 425
4. Zorilla E.P., and Koob G.F. Expert Opin. Invest. Drugs 13 (2004) 799
5. Schulz D.W., Mansbach R.S., Sprouse J., Braselton J.P., Collins J., Corman M., Dunaiskis A., Faraci S., Schmidt A.W., Seeger T., Seymour P., Tingley III F.D., Winston E.N., Chen Y.L., and Heym J. Proc. Natl. Acad. Sci. U.S.A. 93 (1996) 10477
6. He L., Gilligan P.J., Zaczek R., Fitzgerald L.W., McElroy J., Shen H.S., Saye J.A., Kalin N.H., Shelton S., Christ D., Trainor G., and Hartig P. J. Med. Chem. 43 (2000) 449
7. Liaw C.W., Grogoriadis D.E., Lorang M.T., De Souza E.B., and Maki R.A. Mol. Endocrinol. 11 (1997) 2048
8. Hoare S.R.J., Brown B.T., Santos M.A., Malany S., Betz S.F., and Grigoriadis D.E. Biochem. Pharmacol. 72 (2006) 244
9. St-Denis Y., Di Fabio R., Bonanomi G., Capelli A.M., Castiglioni E., Contini S., Degiorgis F., Di Felice P., Donati D., Fazzolari E., Gentile G., Marchionni C., Marchioro C., Messina F., Micheli F., Pavone F., Pasquarello A., Perini B., Rinaldi M., Sabbatini F.M., Zarantonello P., Arban R., and Vitulli G. ChemMedChem 2 (2007) 528
10. Meade E.A., and Beauchamp L.M. J. Heterocycl. Chem. 33 (1996) 303
11. Mahadevan I., and Rasmusen M. J. Heterocycl. Chem. 29 (1992) 359
12. Harris, M. C.; Buchwald, S. L. J. Org. Chem. 2000, 17, 5327.
13. For a detailed description of the in vitro assay used for the characterization of the molecules prepared, see the experimental section in Ref. 9.
14. PK profile was measured in Sprague-Dawley male rats (n = 3), after po (1 mg/kg, dose) and iv (0.4 mg/kg dose) administration. For experimental details, see Ref. 9.
15. 3) δ ppm 8.05 (d, 1H), 7.90 (d, 1H), 7.80 (dd, 1H), 6.57 (s, 1H), 6.49 (s, 1H), 3.89 (t, 2H), 3.87 (m, 1H), 3.08 (m, 2H), 2.43 (s, 3H), 1.85 (m, 4H), 0.81 (t, 6H).